Systems and methods for measuring oxygenation or hemoglobin concentration

ABSTRACT

Optoacoustic diagnostic systems, devices, and methods are described. A system may comprise a console unit and a handheld probe. The console unit comprises a controller, a processor, a photodiode array, an acoustic processing subsystem, and a cooling subsystem. The probe directs light signals from the photodiode array to patient tissue. The light signals each have different wavelengths selected based on the physiological parameter of interest. The probe further comprises an acoustic transducer that receives acoustic signals generated in response to the directed light signals. The probe may comprise a finger-held working end that can be directed to the skull of a fetus within the uterus during labor. The probe can then accurately determine blood oxygenation of the fetus to determine if a caesarian section is necessary.

CROSS-REFERENCE

This application is a continuation U.S. patent application Ser. No.14/794,037, filed Jul. 8, 2015, now U.S. patent Ser. No. ______, whichclaims the benefit of U.S. Provisional Application Nos. 62/021,946,filed Jul. 8, 2014, and 62/168,081, filed May 29, 2015, the fulldisclosures of which are incorporated herein by reference.

The subject matter of this application is related to the subject matterof the following patents and patent applications: U.S. Pat. No.6,309,352, issued Oct. 27, 1998 and entitled “Real Time OptoacousticMonitoring of Changes in Tissue Properties,” U.S. Pat. No. 6,498,942,issued Dec. 24, 2002 and entitled “Optoacoustic Monitoring of BloodOxygenation,” U.S. Pat. No. 6,725,073, issued Apr. 20, 2004 and entitled“Methods for Noninvasive Analyte Sensing,” U.S. Pat. No. 6,751,490,issued Jun. 15, 2004 and entitled “Continuous Optoacoustic Monitoring ofHemoglobin Concentration and Hematocrit,” U.S. Pat. No. 7,430,445,issued Sep. 30, 2008 and entitled “Noninvasive Blood Analysis by OpticalProbing of the Veins Under the Tongue,” U.S. Pat. No. 8,135,460, issuedMar. 13, 2012 and entitled “Noninvasive Glucose Sensing Methods andSystems,” U.S. Pat. No. 8,352,005, issued Jan. 8, 2013 and entitled“Noninvasive Blood Analysis by Optical Probing of the Veins Under theTongue,” and U.S. Pat. No. 9,380,967, issued Jul. 5, 2016 and entitled“Systems and Methods for Measuring Cerebral Oxygenation,” and U.S.patent application Ser. No. 12/101,891, filed Apr. 11, 2007 and entitled“Optoacoustic Monitoring of Multiple Parameters,” Ser. No. 13/538,687,filed Jun. 29, 2012 and entitled “Noninvasive, Accurate GlucoseMonitoring with OCT by using Tissue Warming and Temperature Control,”and Ser. No. 14/794,022, filed Jul. 8, 2015 and entitled “Systems andMethods for Measuring Oxygenation,” the full disclosures of which arefully incorporated herein by reference.

NOTICE OF GOVERNMENT-SPONSORED RESEARCH

This invention was made with Government support under grant/contractnumber 1R43HD075551-01, awarded by the National Institutes of Health(NIH). The Government has certain rights in the invention.

BACKGROUND

Cerebral hypoxia during labor represents a risk factor for death orsevere neurologic complications (e.g., cerebral palsy). At present,there are no commercially available monitors that can be used to detectcerebral hypoxia, other than fetal heart rate (FHR) monitors that usechanges in basal heart rate and changes in FHR variability and timing ofFHR decelerations to indirectly assess fetal asphyxia. Although fetalheart rate monitoring provides important information regarding fetaloxygenation, this information is somewhat limited and provides noinformation regarding the risk of cerebral palsy. As a consequence, manycesarean sections are performed as a defensive measure to reduce therisk of intrapartum fetal asphyxia by reducing the duration of labor.Unfortunately, defensive cesarean sections entail added maternal risk.Maternal death rates are 21% higher in states with cesarean sectionrates exceeding 33% than those with rates less than 33%.

In view of the limited information provided by FHR and the risksassociated with cesarean procedures, it can be appreciated that it wouldbe desirable to have a more direct way of measuring fetal cerebraloxygenation (i.e., hemoglobin saturation).

References that may be of interest include: U.S. Pat. Nos. 4,537,197,5,088,493, 5,099,842, 5,228,440, 5,348,002, 5,377,673, 5,823,952,5,840,023, 5,941,821, 6,049,728, 6,381,480, 6,553,242, 6,594,515,6,463,311, 6,466,806, 6,484,044, 6,567,678, 6,751,490, 6,846,288,7,164,938, 7,322,972, 7,515,948, 7,747,301, 7,916,283, 8,121,663,8,280,469, 8,332,006, 8,423,111, 8,501,099, 8,781,548, 8,852,095,8,864,667, 8,885,155, 8,930,145, and 8,934,953; U.S. Publication Nos.2006/100530, 2006/184042, 2007/015992, 2009/069652, 2009/108205,2010/081904, 2011/239766, 2013/112001, 2013/190589, 2013/324815,2014/142404, 2014/275943, 2014/343384, 2014/378811, 2015/051473, and2015/099973; German Patent Publication No. DE 4400674 A1; and,“Noninvasive monitoring of cerebral blood oxygenation in ovine superiorsagittal sinus with novel multi-wavelength optoacoustic system” toPetrova et al. (27 Apr. 2009/Vol. 17, No. 9/OPTICS EXPRESS 7285).

SUMMARY

The present disclosure relates generally to medical devices and methodsfor their use, and particularly optoacoustic diagnostic devices andmethods. Systems, devices, and methods to determine one or morephysiological parameters optoacoustically are described. An exemplarysystem may comprise a convenient, desktop-sized console unit comprisinga controller and/or a processor, a photodiode array, an acousticprocessing subsystem, and a cooling subsystem. The system may furthercomprise a handheld probe that can be coupled to the console unit. Theprobe may direct light signals from the photodiode array of the consoleunit to patient tissue. A plurality of light signals, each havingdifferent wavelengths, may be directed to the tissue. The wavelengths ofthe light may be selected based on the physiological parameter(s) ofinterest. The probe may further comprise an acoustic transducer thatreceives acoustic signals generated in response to the directed lightsignals. The probe may have various form factors. For example, the probemay comprise a finger-held working end that can be directed to the skullof a fetus within the uterus during labor. The probe can then accuratelydetermine blood oxygenation of the fetus to determine if a caesarianprocedure is necessary, thereby improving outcomes for the mother andchild during labor and reducing malpractice lawsuits and premiums. Theconsole unit can show the blood oxygenation levels (and/or otherphysiological parameter(s)) of the fetus or other target tissue andcommunicate with other computerized healthcare systems, such aselectronic health care records, to record and analyze blood oxygenationreadings or other measured physiological parameters.

Aspects of the present disclosure provide apparatuses, such as adesktop-sized console, for monitoring oxygenation of a subject. Theconsole may comprise a laser diode subsystem for emitting light pulsesdirected to tissue of a subject and an acoustic sensor subsystem formeasuring acoustic pressure generated in the tissue in response to theemitted light pulses. The laser diode subsystem may comprise a firstlaser diode with a first laser diode driver, a first temperaturecontroller with a first thermoelectric cooler and a first temperaturesensor, a second laser diode, a second temperature controller with asecond thermoelectric cooler and a second temperature sensor, a firstcooling fan, and a laser controller. The first laser diode may beconfigured to emit a first light pulse having a first wavelength. Thefirst thermoelectric cooler may be coupled to the first laser diode toadd or remove heat to regulate a temperature of the first laser diode,which may be detected by the first temperature sensor. The second laserdiode may be configured to emit a second light pulse having a secondwavelength different from the first wavelength. The secondthermoelectric cooler may be coupled to the second laser diode to add orremove heat to regulate a temperature of the second laser diode, whichmay be detected by the second temperature sensor. The first and secondtemperature controllers may be coupled to the first cooling fan and thefirst and second thermoelectric coolers to control the first coolingfan, the first thermoelectric cooler, and the second thermoelectriccooler to regulate the temperatures of the first and second laserdiodes. The first and second temperature controllers may be configuredto keep the first and second laser diodes in an optimal temperaturerange such that the first and second laser diodes can consistently emitlight pulses at the desired wavelengths. Oxygenation of the subject maybe determined in response to the received acoustic pressure.

The laser diode subsystem may further comprise a third laser diode and athird temperature controller, which may comprise a third temperaturesensor and a third thermoelectric cooler. The third laser diode may beconfigured to emit a third light pulse having a third wavelengthdifferent from the first and second wavelengths. The thirdthermoelectric cooler may be coupled to the third laser diode toregulate a temperature of the third laser diode. The third temperaturesensor may be further coupled to the third thermoelectric cooler toregulate the temperature of the third laser diode.

The first temperature controller may comprise the first thermoelectriccooler and the first temperature sensor to measure and control thetemperature of the first laser diode. The second thermoelectriccontroller may comprise a second thermoelectric cooler and a secondtemperature sensor to measure and control the temperature of the secondlaser diode. And, the third temperature controller may comprise thethird thermoelectric cooler and the third temperature sensor to measureand control the temperature of the third laser diode. The first, second,and/or third temperature controllers may be configured to regulate thetemperatures of the first, second, and/or third laser diodes in responseto the temperatures measured by the first, second, and third temperaturesensors, respectively. The first, second, or third wavelength may be ina range of 685 nm to 715 nm, 715 nm to 745 nm, 745 nm to 775 nm, 790 nmto 820 nm, or 845 nm to 875 nm.

The console may further comprise a processor coupled to the laser diodesubsystem to control the laser diode subsystem and coupled to theacoustic sensor subsystem to receive the measured acoustic pressure. Theprocessor may be configured to determine oxygenation of the subject inresponse to the measured acoustic pressure. The console may furthercomprise a power supply coupled to the laser diode subsystem, theacoustic sensor subsystem, and the processor. The console may furthercomprise a display coupled to the processor to display the determinedoxygenation to a user. The display may comprise a touch screen foroperating the console. The console may further comprise a desktop-sizedhousing enclosing the laser diode subsystem, the acoustic sensorsubsystem, and the processor. The console may further comprise a secondcooling fan, which may be coupled to one or more of the processor oracoustic sensor subsystem, for cooling the console. The processor may becapable of accessing medical records of the subject.

The console may further comprise an output port for the laser diodesubsystem and an input port for the acoustic sensor subsystem. Theoutput port and the input port may be configured to be coupled to asensor module or an optoacoustic probe to emit the one or more lightpulses to the tissue of the subject and to receive the acoustic pressuregenerated in the tissue. The output port and the input port may beconfigured to be coupled to the sensor module or optoacoustic probe witha cable comprising one or more optical fibers.

Aspects of the present disclosure also provide methods of monitoringoxygenation of a subject. A first light pulse having a first wavelengthmay be generated with a first laser diode. A second light pulse having asecond wavelength different from the first wavelength may be generatedwith a second laser diode. The temperatures of the first and secondlaser diodes may be regulated with a first thermoelectric cooler coupledto the first laser diode, a second thermoelectric cooler coupled to thesecond laser diode, and/or a first cooling fan. The generated first andsecond light pulses may be directed to tissue of a subject. Acousticpressure generated in the tissue in response to the directed first andsecond light pulses may be measured. Oxygenation of the subject may bedetermined in response to the measured acoustic pressure.

A third light pulse having a third wavelength different from the firstand second wavelengths may be generated with a third laser diode. Atemperature of the third laser diode may be regulated with a thirdthermoelectric cooler coupled to the third laser diode and the firstcooling fan. The generated third light pulse may be directed to thetissue of the subject. The measured acoustic pressure may be generatedin the tissue in response to the directed first, second, and third lightpulses.

The first temperature controller may comprise a first temperature sensorto measure the temperature of the first laser diode and a firstthermoelectric cooler to add or remove heat to regulate the temperatureof the first laser diode in response to the measured temperature. Thesecond temperature controller may comprise a second temperature sensorto measure the temperature of the second laser diode and a secondthermoelectric cooler to add or remove heat to regulate the temperatureof the second laser diode in response to the measured temperature. And,the third temperature controller may comprise a third temperature sensorto measure the temperature of the third laser diode and a thirdthermoelectric cooler to add or remove heat to regulate the temperatureof the third laser diode in response to the measured temperature. Thefirst, second, and third temperature controllers may be configured toregulate the temperatures of the first, second, and third laser diodesin response to the temperatures measured by the first, second, and thirdtemperature sensors, respectively. The first, second, or thirdwavelength may be in a range of 685 nm to 715 nm, 715 nm to 745 nm, 745nm to 775 nm, 790 nm to 820 nm, or 845 nm to 875 nm.

The determined oxygenation of the subject may be displayed. Thetemperatures of the first, second, and/or third laser diodes may beregulated with a second cooling fan. The second cooling fan may beenclosed within a housing enclosing the first laser diode, the secondlaser diode, the third laser diode, and/or the first cooling fan. Thegenerated first and second light pulses may be directed to tissue of thesubject by directing the first and second light pulses with an opticalwaveguide of a sensor module or an optoacoustic sensor coupled to thefirst and second photodiodes. The acoustic pressure may be measured byan acoustic transducer of the sensor module or the optoacoustic sensor.

Aspects of the present disclosure also provide methods foroptoacoustically determining oxygenation of a subject. A first lighthaving a first wavelength may be emitted to tissue of the subject. Asecond light having a second wavelength may be emitted to the tissue.The second wavelength may be different from the first wavelength. Athird light having a third wavelength may be emitted to the tissue. Thethird wavelength may be different from the first and second wavelengths.Acoustic pressure generated by the tissue in response to the first,second, and third emitted lights may be detected.

The first wavelength may be in a range from 790 to 820 nm, such as 800nm or 805 nm. The second or third wavelength may be in a range from 685nm to 715 nm, 715 nm to 745 nm, 745 nm to 775 nm, or 845 nm to 875 nm,such as 700 nm, 730 nm, 760 nm, or 860 nm, for example.

The first, second, and third lights may be emitted from a common lightsource. The common light source may be configured to rapidly switchbetween emitting the first light with the first wavelength, the secondlight with the second wavelength, and the third light with the thirdwavelength. For example, the common light source may be a commonlycontrolled laser diode array or an optical parametric oscillator (OPO).The first, second, and third lights may be emitted to the tissue from acommon optical fiber.

One or more of the first, second, or third lights may have an energylevel of at least 0.5 microjoules. One or more of the emitted first,second, or third lights may have a pulse width of at least 100 ns. Oneor more of the emitted first, second, or third lights may have arepetition rate of 10 to 10,000 Hz.

Oxygenation may be determined in response to the detected acousticpressure by determining oxygenation in response to a first difference indetected acoustic pressure in response to the first emitted light and inresponse to the second emitted light and a second difference in detectedacoustic pressure in response to the first emitted light and in responseto the third emitted light. Oxygenation may be determined by determiningoxygenation in response to an average of oxygenation determined inresponse to the first difference and oxygenation determined in responseto the second difference. The first wavelength may have substantiallyequal absorption between oxyhemoglobin and deoxyhemoglobin. The secondand third wavelengths may have absorption differences betweenoxyhemoglobin and deoxyhemoglobin.

Aspects of the present disclosure also provide systems foroptoacoustically determining oxygenation of a subject. The system mayfurther comprise a light source, an acoustic transducer, and aprocessor. The light source may be configured to emit to tissue a firstlight having a first wavelength, a second light having a secondwavelength different from the second wavelength, and a third lighthaving a third wavelength different from the first and secondwavelengths. The acoustic transducer may be configured to detectacoustic pressure generated by the tissue in response to the first,second, and third emitted lights. The processor may be configured todetermine oxygenation in response to the detected acoustic pressure.

The light source may comprise an array of laser diodes or light emittingdiodes. The array of laser diodes or light emitting diodes may comprisea first laser diode configured to emit the first light, a second laserdiode configured to emit the second light, and a third laser diodeconfigured to emit the third light. The first wavelength may be in arange from 790 to 820 nm, such as 805 nm. The second or third wavelengthmay be in a range from 685 nm to 715 nm, 715 nm to 745 nm, 745 nm to 775nm, or 845 nm to 875 nm, such as 700 nm, 730 nm, 760 nm, or 860 nm, forexample.

The system may further comprise a controller configured to rapidlyswitch the light source between emitting the first light with the firstwavelength, the second light with the second wavelength, and the thirdlight with the third wavelength. For example, the light source may be acommonly controlled laser diode array or an optical parametricoscillator (OPO). The first, second, and third lights may be emitted tothe tissue from a common optical fiber.

One or more of the first, second, or third lights may have an energylevel of at least 0.5 microjoules. One or more of the emitted first,second, or third light may have a pulse width of at least 150 ns. One ormore of the emitted first, second, or third light may have a repetitionrate of 10 to 2000 Hz.

The processor may be configured to determine oxygenation in response toa first difference in detected acoustic pressure in response to thefirst emitted light and in response to the second emitted light and asecond difference in detected acoustic pressure in response to the firstemitted light and in response to the third emitted light. The processormay be configured to determine oxygenation in response to an average ofoxygenation determined in response to the first difference andoxygenation determined in response to the second difference. The firstwavelength may have substantially equal absorption between oxyhemoglobinand deoxyhemoglobin. The second and third wavelengths may haveabsorption differences between oxyhemoglobin and deoxyhemoglobin. Thesystem may further comprise a display configured to display thedetermined oxygenation.

Aspects of the present disclosure may also provide methods of monitoringoxygenation of a fetus, such as venous oxygenation of the fetus. Asensor may be inserted into a vagina. The sensor may comprise a lightoutput and an acoustic transducer. The sensor may be advanced through acervix and into a uterus. The sensor may be positioned over a head ofthe fetus. The light output of the sensor may emit light to the head ofthe fetus and the acoustic transducer of the sensor may detect acousticpressure generated in response to the emitted light. The sensor maydetermine oxygenation of the fetus in response to the detected acousticpressure.

The sensor may comprise a probe head, which may be inserted into thevagina. The sensor may comprise an oxygenation monitor configured todisplay the determined oxygenation of the fetus and a cable connectingthe probe head with the oxygenation monitor. The oxygenation monitor andat least a portion of the cable may remain outside the uterus as theprobe head is inserted into the vagina. The light output may comprise awaveguide in the probe head. The cable may comprise one or more opticalfibers and the oxygenation monitor may comprise one or more laser diodesor light emitting diodes coupled to the waveguide through the one ormore optical fibers. To insert the sensor into the vagina, the probehead may be grasped between two finger tips of a user. The sensor may bepositioned over a head of the fetus by positioning the light output andthe acoustic transducer to face a superior sagittal sinus of the fetus.To position the sensor over a head of the fetus comprises, a tip of thelight output extending from the probe head may be contacted with skin ofthe head of the fetus, such as to pass through hair to reduce loss oflight intensity due to absorption by the hair.

The light output of the sensor may emit light to a superior sagittalsinus of the fetus. The acoustic pressure generated in response to theemitted light may be generated by the superior sagittal sinus. Thesensor may determine oxygenation of the superior sagittal sinus. Thesensor may be inserted into the vagina/birth canal and uterus duringlabor.

The light emitted by the light output may have an energy of 1 μJ to 1mJ. The light emitted by the light output may have wavelengths in rangeof two or more of 685-715 nm, 715-745 nm, 745-775 nm, 790-820 nm, or845-875 nm, such as wavelengths in range of two or more of 700 nm, 730nm, 760 nm, 805 nm, or 860 nm.

Aspects of the present disclosure may also provide further methods ofmonitoring oxygenation of a fetus, such as venous oxygenation of thefetus. Light may be emitted from a light output of a sensor positionedover a head of a fetus in a uterus. Acoustic pressure may be detectedwith an acoustic transducer of the sensor. The acoustic pressure may begenerated in response to the emitted light. Oxygenation of the fetus maybe determined in response to the detected acoustic pressure. Thedetermined oxygenation of the fetus may be displayed to the user withthe sensor.

The sensor may comprise a probe head comprising the light output andacoustic transducer. The light output may comprise a tip extending outfrom a housing of the probe head. The sensor may comprise an oxygenationmonitor configured to display the determined oxygenation of the fetusand a cable connecting the probe head with the oxygenation monitor. Thelight output may comprise a waveguide, such as an optical fiber, in theprobe head. The cable may comprise one or more optical fibers and/orelectrical cables. The oxygenation monitor may comprise one or morelaser diodes or light emitting diodes coupled to the waveguide throughthe one or more optical fibers and/or other optical components such asmirrors or lenses. The electrical cable(s) may connect the acoustictransducer in the probe head to the oxygenation monitor.

The light output and the acoustic transducer may be positioned to face asuperior sagittal sinus of the fetus. The light output of the sensor mayemit light to a superior sagittal sinus of the fetus. The acousticpressure generated in response to the emitted light may be generated byblood in the superior sagittal sinus. The sensor may determine theoxygenation of venous blood in the superior sagittal sinus.

The light emitted by the light output may have an energy of 1 μJ to 1mJ. The light emitted by the light output may have wavelengths in rangeof two or more of 685-715 nm, 715-745 nm, 745-775 nm, 790-820 nm, or845-875 nm, such as wavelengths in range of two or more of 700 nm, 730nm, 760 nm, 800 nm, 805 nm, or 860 nm.

Aspects of the present disclosure also provide systems for monitoringoxygenation of a fetus, such as venous cerebral oxygenation of thefetus. The system may comprise a monitor, a cable, and a probe head. Themonitor may comprise a processor, a light source, and a display. Theprobe head may be configured to be held between two finger tips of auser and coupled to the monitor through the cable. The probe head maycomprise a light output and an acoustic transducer. The light source maybe configured to generate a light emitted to the fetus through the lightoutput of the probe head. The acoustic transducer may be configured todetect acoustic pressure generated in response to the emitted light. Theprocessor may be configured to determine oxygenation of the fetus inresponse to the detected acoustic pressure. The display may beconfigured to display the determined oxygenation. The light output maycomprise a tip extending out from a housing of the probe head.

The light source of the monitor may comprise one or more laser diodes orlight emitting diodes. The light source of the monitor may be configuredto generate light having an energy of 1 μJ to 1 mJ. The light source ofthe monitor may be configured to generate light having wavelengths inrange of two or more of 685-715 nm, 715-745 nm, 745-775 nm, 790-820 nm,or 845-875 nm, such as two or more of 700 nm, 730 nm, 760 nm, 800 nm,805 nm, or 860 nm, for example. The cable may comprise one or moreoptical fibers configured to direct light generated by the light sourceto the light output of the probe head.

Aspects of the present disclosure may also provide fetal cerebral venousoxygenation probes. A fetal cerebral venous oxygenation probe maycomprise a probe head and a cable. The probe head may include a lightoutput configured to emit light into a head of the fetus and an acoustictransducer configured to detect acoustic pressure generated in responseto the emitted light. The cable may extend out of the probe head to amonitor.

The probe head may be adapted to be held between two finger tips of auser. The probe head may be cylindrical. The light output may comprise atip or output extending out from a housing of the probe head, such asfrom a center of the probe head. For example, the tip or output maycomprise a protrusion of the optical fiber coupled to the light source.The light output may comprise an optical waveguide comprising acontinuous rounded groove encircling a center of the probe head. Theprobe head may comprise a housing defining an interior space where theacoustic transducer is positioned and through which the light outputpasses. The light output may comprise one or more optical fibers. Theacoustic transducer may comprise a piezoelectric transducer. The probehead may further comprise an amplifier for the acoustic transducer. Theprobe head may further comprise an electromagnetic shield that shieldsthe acoustic sensor and amplifier from electromagnetic interference. Theprobe head may further comprise an acoustic attenuator configured toabsorb undesired ringing in the probe head. The light output may beconfigured to channel light generated by a light source in the monitor.

The probe head may be configured to emit light having an energy of 10 to1 mJ. The light emitted by the light output may have wavelengths inrange of two or more of 685-715 nm, 715-745 nm, 745-775 nm, 790-820 nm,or 845-875 nm, such as two or more of 700 nm, 730 nm, 760 nm, 805 nm, or860 nm, for example.

INCORPORATION BY REFERENCE

All publications, patents, and patent applications mentioned in thisspecification are herein incorporated by reference to the same extent asif each individual publication, patent, or patent application wasspecifically and individually indicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the present disclosure are set forth withparticularity in the appended claims. A better understanding of thefeatures and advantages of the present disclosure will be obtained byreference to the following detailed description that sets forthillustrative embodiments, in which the principles of the invention areutilized, and the accompanying drawings. Matching reference numeralsdesignate corresponding parts throughout the figures, which are notnecessarily drawn to scale.

FIG. 1 shows a schematic diagram of a system for optoacoustic diagnosisof one or more physiological parameters, according to many embodiments.

FIG. 2 shows a schematic diagram of an exemplary laser diode subsystemof the system of FIG. 1.

FIG. 3 is a schematic view of an embodiment of a system for measuringfetal cerebral oxygenation, according to many embodiments.

FIG. 4 is a perspective view of an embodiment of a fetal cerebraloxygenation probe that can be used in the system of FIG. 3, according tomany embodiments.

FIG. 5 is a front view of the fetal cerebral oxygenation probe of FIG.4.

FIG. 6 is a side view of the fetal cerebral oxygenation probe of FIG. 4.

FIG. 7 is a cross-sectional side view of the fetal cerebral oxygenationprobe of FIG. 4.

FIG. 8 is a schematic view illustrating a first example grip used tohold a fetal cerebral oxygenation probe during a fetal examination,according to many embodiments.

FIG. 9 is a schematic view illustrating a second example grip used tohold a fetal cerebral oxygenation probe during a fetal examination,according to many embodiments.

FIG. 10A is a graph that plots optoacoustic signals recorded from thesuperior sagittal sinus (SSS) of a first baby at various wavelengths,according to many embodiments.

FIG. 10B is a graph that plots typical optoacoustic signals recordedfrom the SSS of a second baby at various wavelengths, according to manyembodiments.

FIGS. 11A and 11B illustrate an exemplary configuration of anoptoacoustic probe, according to many embodiments.

FIGS. 12A and 12B illustrate another exemplary configuration of anoptoacoustic probe, according to many embodiments.

FIGS. 13A, 13B, and 13C illustrate a probe as grasped by a user during afetal cerebral oxygenation measurement procedure, according to manyembodiments.

FIGS. 14A, 14B, and 14C illustrate another probe as grasped by a userduring a fetal cerebral oxygenation measurement procedure, according tomany embodiments.

FIGS. 15A and 15B illustrate yet another probe as grasped by a userduring a fetal cerebral oxygenation measurement procedure, according tomany embodiments.

FIG. 16 shows a flowchart of an exemplary method to measure or detectone or more physiological parameters optoacoustically, according to manyembodiments.

FIGS. 17A, 17B, and 17C illustrate an exemplary configuration of anoptoacoustic probe, according to many embodiments.

FIG. 18A is a graph that plots differential optoacoustic signalsrecorded from a fetus during late stage labor, according to manyembodiments.

FIG. 18B is a graph that plots differential optoacoustic signalsrecorded from a fetus during late stage labor, according to manyembodiments.

DETAILED DESCRIPTION

As described above, it would be desirable to have a direct way ofmeasuring fetal cerebral oxygenation, such as cerebral venous bloodoxygenation saturation. Disclosed herein are systems and methods thatare well suited for this purpose. In many embodiments, a system formeasuring fetal cerebral oxygenation comprises a fetal cerebraloxygenation probe that can be applied to the fetus' head during labor.The probe can be an optoacoustic probe that is configured to emit lightthrough the skull and brain tissue to the superior sagittal sinus (SSS)and receive back acoustic waves that are induced by the irradiation ofthe SSS. A determination of the blood oxygen saturation can then be madefrom the acoustic waves. In some embodiments, the probe is sized andconfigured to fit between the fingers of an obstetrician to facilitateapplication to the fetus' head and comprises a wave guide that emits thelight and an acoustic sensor that detects the acoustic signal emittedfrom the SSS.

In the following disclosure, various specific embodiments are described.It is to be understood that those embodiments are exampleimplementations of the disclosed inventions and that alternativeembodiments are possible. All such embodiments are intended to fallwithin the scope of this disclosure.

Disclosed herein are systems and methods for monitoring cerebraloxygenation that can be used to perform accurate, noninvasivemeasurement of cerebral venous blood oxygen saturation in fetuses duringlate-stage labor through the open anterior fontanelle or through thethin cranial bones. Cerebral venous oxygen saturation provides in asingle number an assessment of the ability of cerebral blood flow andcerebral blood oxygen content to meet cerebral oxygen requirements. Asdescribed below, the systems and methods enable optoacoustic measurementin the superior sagittal sinus (SSS). Such a measurement techniqueprovides high contrast and high resolution that enables direct probingof blood vessels. Because cerebral venous desaturation provides directevidence that cerebral oxygen availability is insufficient to satisfycerebral oxygen requirements, decreasing SSS oxygenation (SSS(SO₂)) canprovide an early warning of cerebral hypoxia. Therefore, this techniquecan be used to directly detect fetal asphyxia more rapidly than fetalheart rate (FHR) monitoring, thereby reducing the risk of cerebralpalsy. This technique is also more specific than FHR monitoring, therebyreducing false-positive incidents of fetal distress and encouragingfewer defensive cesarean sections.

In contrast to previously studied techniques for assessing fetalviability during late-stage labor, optoacoustic monitoring of fetalSSS(SO₂) during labor offers major advantages. In virtually all fetuses,the anterior fontanelle is palpable by vaginal examination once thematernal cervix has dilated to greater than 5 cm and virtually all fetaldistress (detected by FHR monitoring only) occurs after that time. Ininfants, unlike adults, the sagittal sinus is directly below the scalpeither without intervening skull or with thin overlying cranial bones,so relatively low-intensity light penetrates well. Because the generatedultrasound signal returns in a straight line from the SSS, the actualsaturation of hemoglobin in the SSS can be accurately determined. Whilesystems and methods for venous blood oxygenation detection aredescribed, these systems and methods are equally applicable to detectarterial or other blood oxygenation.

FIG. 1 shows a schematic diagram of a system 100 for optoacousticallymeasuring physiological parameters such as blood oxygenation, forexample, fetal cerebral oxygenation (e.g., fetal SSS(SO₂)) during laboror cerebral oxygenation generally such as for a patient with traumaticbrain injury. The system 100 may comprise a console 110 and a patientinterface 150 operatively coupled with a wire or cable connection 145.The console 110 may comprise a console comprising one or more subsystemsor components configured to provide measurement of fetal cerebraloxygenation in a patient PA via the patient interface 150. The console110 may comprise a computer board or processor 115, a user interface120, a power supply subsystem 130, a laser emitter or diode subsystem135, and an acoustic sensor subsystem 140. The processor 115 may be incommunication with the one or more subsystems or components of theconsole 110, so as to control and monitor the operation of thesubsystems. For example, the processor may comprise one or moreuniversal serial bus (USB) ports or other types of data transfer portsconfigured to connect to the one or more subsystems. The processor 115may further comprise an audio port to output alarms and message(s)through a speaker. The power supply subsystem 130 may be configured toprovide power to one or more components of the system 110, such as theprocessor, user interface, laser diode subsystem, and acoustic sensorsubsystem. The power supply subsystem 130 may be configured to connectto an external AC or DC power source and may comprise a battery toprovide back-up power in case of loss of external power.

A user of the system 100, such as medical personnel trained to operatethe system, can interact with the system via the user interface 120. Theuser interface 120 may, for example, comprise a display 125 such as abacklit LCD with a touch screen configured to receive one or more inputsfrom the user. The user interface 120 may further comprise hardwarecontrols for controlling the operation of the system, such as on/offkeys and a stop switch configured to put the system in a “safe” mode,wherein all laser diodes are turned off. The user interface 120 may alsocomprise an input for data such as patient identification, time,temperature, etc. The processor 115 can receive user input via the userinterface 120, and transmit instructions based on the user input to oneor more subsystems, such as the laser diode subsystem 135, acousticsensor subsystem 140, and/or power supply subsystem 130. Based oninstructions received from the processor 115, the laser diode subsystem135 may generate and emit light pulses which may be directed to a targettissue of the patient PA through the patient interface 150. The lightpulses can be conducted through the cable connection 145, such as afiber optic cable and/or a multiwire shielded cable, to the patientinterface 150. For example, the light pulses can be transmitted to anoptical fiber module of the patient interface 150 that is in contactwith the target tissue, such as the superior sagittal sinus (SSS). Thelight pulses can pass through the tissue and bone to the venous blood,wherein absorption of the light pulses can result in the generation ofacoustic pressure. The patient interface 150 can detect the acousticpressure from the target tissue and transmit the acoustic signals backto the console 110, for example via the cable connection 145 to theacoustic sensor subsystem 140. The patient interface 150 can comprise,for example, a high speed digitizer configured to detect and digitizethe acoustic pressure. The acoustic sensor subsystem 140 can receiveand/or at least partially process the measured acoustic pressure signalsthen digitize the signals, and transmit the signals to the processor 115for further processing and analysis. The processor 115 can, for example,compute the venous oxygen saturation from the measured acousticpressure, and transmit results of the measurement to the user interface120 to be displayed to the user via the display 125. The display 125 maybe configured to display oxygen saturation readings (e.g., venous oxygensaturation readings) or other physiological parameters continuously,with updates once per minute, for example. In some embodiments, thesystem 100 may further comprise a communications subsystem tocommunicate with other electronic or computerized healthcare managementsystems. For example, the physiological parameter data measured may bestored and archived (to generate electronic medical records) andanalyzed with another computerized system in communication with thesystem 100.

The system 100 may be configured to have a compact size to accommodatelimited spaces available in transport vehicles, forward aid stations, orintensive care units. For example, the console 110 may be desktop-sized.Components of the system 100 may be ergonomically designed so as toallow easy operation for medical personnel who may be generallyunfamiliar with optoacoustic measurements. The display 125 of the system100 can provide user guidance for use of the system 100, as well asdisplay the status of various alarms of the system 100, in order to helpusers understand causes of the alarms and take appropriate remedialactions. The system 100 may be configured to allow up to about 24 hoursof continuous monitoring without changing locations. A power loss alarmmay be implemented with the system 100, in order to alert the user ofsignal loss or cable disconnection during monitoring. The system 100 mayfurther be configured to have a user-selectable transport mode that cansupport battery-operated use of the system 100 for up to about one hour.In the transport mode, the system 100 may be configured to operate withlow power (e.g., lower power than in the operational mode), and thepower loss alarm may be disabled. The system 100 may be furtherconfigured to allow users to input patient identification data, accesspatient medical records, and download the measurement data collectedduring the monitoring process for archival and evaluation purposes, forexample through the communications subsystem described above.

The system 100 may be configured to monitor various physiologicalparameters. In many embodiments, oxygen saturation is measured. Forexample, venous oxygen saturation in the range from about 20% to about100% (calculated as oxyhemoglobin÷total hemoglobin concentration [THb],as described further herein) may be measured. The system 100 may have anaccuracy of about +/−3% over the saturation range from about 40% toabout 90%, for example.

The acoustic sensor subsystem 140 may receive acoustic signals from thepatient interface 150. The acoustic sensor subsystem 140 may comprise aone or more signal amplifiers configured to provide a gain for thereceived signals. The gain may be, for example, about 40 dB of gain at500 kHz and may have, for example a −3 dB bandwidth of 50 kHz to 3.5Mhz. The acoustic sensor subsystem 140 may comprise a high speeddigitizer that may sample the amplified acoustic signal from theamplifier. This sampling may be performed at a minimum rate 20 MHz, forexample. The digitizer may receive a trigger signal from the laser diodesubsystem 135 and store samples, such as a 100, 200, 300, 400, 500, 600,700, 800, 900, or 1000 samples, of the acoustic signal. The digitizermay transfer the block of samples to the processor 115 for waveformaveraging. Often, the acoustic signals generated by the target tissue islow level and averaging readings over hundreds of repetitive cycles canextract the waveform out of background noise.

The patient interface 150 may comprise an optoacoustic sensor assemblyor sensor module, such as the cerebral oxygenation probe 20 as describedin further detail herein. An optoacoustic sensor assembly can comprise alight output configured to emit light pulses directed at the targettissue, and an acoustic transducer configured to measure the acousticpressure generated in response to the light pulses. The light output mayoutput light from a light source. The light source may comprise, forexample, a light emitting diode (LED) array or a high power pulsed laserdiode array configured to generate high intensity light pulses at one ormore wavelengths. The light output can be connected to the console 110via a fiber optic cable, for example. The light source may comprise thelaser diode subsystem 135 of the console 110. The acoustic transducercan comprise, for example, a piezoelectric sensor, connected to theconsole via a multiwire shielded cable. The cables 145 connecting thepatient interface 150 and the console 110 may comprise connectors toremovably couple the cables to the console. The light source and theacoustic transducer may be supported with a probe that can be placedover a portion of the patient's head, such as the surface of the scalpover the SSS. The probe 20 may be held in place with a strap system,which may comprise a disposable, single-use mounting strap in order toreduce or eliminate the need for cleaning and disinfection between uses.

FIG. 2 shows a schematic diagram of the laser diode subsystem 135 of thesystem 100 of FIG. 1. The laser diode subsystem 135 may comprise a laserdiode array comprising, for example, a first laser emitter or diode152A1, a second laser emitter or diode 152B1, and a third laser emitteror diode 152C1. The laser diode subsystem 135 may comprise a lasercontrol processor 156 in communication with the processor 115 of theconsole 110 of the system. The laser control processor 156 can receiveinstructions from the console processor 115 based on one or more userinputs provided to the console 110. For example, the processor 115 canset and monitor operational parameters, and start and stop measurementcycles by the laser diode subsystem 135. The laser diode subsystem 135may further comprise a laser supervisor processor 158, in communicationwith the laser control processor. The laser supervisor processor 158 maymonitor the operation of the laser diodes 152A1, 152B1, and/or 152C1 toensure that the temperature of the diodes 152A1, 152B1, and/or 152C1 issubstantially constant or within an acceptable range to maintainwavelength accuracy. For example, an acceptable operational temperaturerange may be from 10° C. to 40° C. Together, the laser control processor156 and the laser supervisor processor 158 can control and monitor theoperation of one or more laser drivers 154. The laser controllers 154can be configured to receive instructions from the laser controlprocessor 156 and the laser supervisor processor 158, and in response tothe received instructions, control operation of the laser emitter ordiodes 158A, 152B1, and/or 152C1 coupled to the laser controllers 154.The laser controllers 154 can further be configured to control operationof one or more laser emitter coolers, such as coolers 152A2, 152B2,and/or 152C2, coupled to and configured to cool the corresponding laseremitters 152A1, 152B1, and/or 152C1, respectively. The laser controllers154 may comprise laser drivers for the laser diodes 152A1, 152B1, and152C1 and their respective coolers 152A2, 152B2, and 152C2. For example,the laser emitter coolers may comprise thermoelectric coolers (TEC)and/or two temperature sensors (primary and secondary) mounted on theback of each laser diode 152A1, 152B1, and/or 152C1. The temperaturesensors can be configured to measure the temperature of the laser diodes152A1, 152B1, and/or 152C1, and the TECs can be configured to controlthe temperature of the laser diodes 152A1, 152B1, and/or 152C1 to keepthem in an optimal operational temperature range, such as by adding orremoving heat depending on the temperature measured and the temperaturerange desired. For example, the wavelengths of the laser diodes 152A1,152B1, and 152C1 may have a dependency of about 0.3 nm/deg C. The laserdrivers may be configured to generate high amperage, short durationcurrent pulses to drive the laser diodes 152A1, 152B1, and 152C1. Thelight pulses generated by the laser emitters 152A1, 152B1, and/or 152C1can be conducted through the cable connection 145 to a patient interface150, which may comprise an optoacoustic sensor assembly or probe asdescribed herein.

The laser diode subsystem 135 can further comprise a cooling fan 160,configured to provide an air stream shown by the arrow 162, directedtowards to the components of the laser diode subsystem 135. Such acooling fan 160 can help control the temperature of the components,which may be disposed in a closed laser cavity to as to prevent dustcontamination of the optical components. The cooling fan 160 may furthercomprise a second fan configured to circulate outside air over thecontrol electronics. The laser cavity may be surrounded by a laser diodesubsystem enclosure, constructed from metal plates. The enclosure of thelaser diode subsystem 135 can be securely mounted to the enclosure forthe console 110, for example via mechanical fasteners.

At start-up, the laser diode subsystem 135 may have a temperaturestabilization time for the laser diodes 152A1, 152B1, and/or 152C1. Thetemperature stabilization status can be displayed on the display 125 ofthe console 110. During operation of the laser diodes 152A1, 152B1,and/or 152C1, the operational parameters of the laser diodes 152A1,152B1, and/or 152C1, including the temperature measurements generated bythe laser emitter coolers 152A2, 152B2 and/or 152C2, can be transmittedback to the laser control processor 156 and/or the laser supervisorprocessor 158, for feedback control of laser diode operation. Forexample, in embodiments wherein the laser emitter coolers comprise a TECand temperature sensors coupled to each laser diode, the laser controlprocessor 156 can comprise instructions to drive current through the TECto control the measured temperature from the temperature sensors.

The laser emitters 152A1, 152B1, and/or 152C1 of the laser diodesubsystem 135 may comprise pulsed laser diodes having nominal centerwavelengths of about 760 nm, 800 nm, and 860 nm, respectively, forexample. Other wavelengths such as 700 nm, 730 nm, 850 nm, 905 nm, 970nm, 975 nm, 1064 nm, 1100 nm, 1200 nm, 1230 nm, and 1450 nm, to name afew, are also contemplated. The wavelengths may be chosen to correspondwith the peak acoustic response of parameters of interest such as water,fat, hemoglobin, oxyhemoglobin, deoxyhemoglobin, carboxyhemoglobin,reduced hemoglobin, methemoglobin, lactate, myoglobin, cholesterol, bodypigments, exogenous dyes such as indocyanine green (ICG), to name a few.While the determination of blood oxygenation is discussed herein, theinterrogation of other physiological parameters and concentrations isalso contemplated. The concurrent determination of two or morephysiological parameters or concentrations is described in U.S.Publication No. 2008/0255433 A1, which is incorporated herein byreference.

The nominal center wavelengths may have a stability of about +/−1 nm,0.9 nm, 0.8 nm, 0.7 nm, 0.6 nm, 0.5 nm, 0.4 nm, 0.3 nm, 0.2 nm, or 0.1nm over the operational temperature range. The spectral width (fullwidth half maximum) of the light output of each laser diode may be about25 nm, 20 nm, 15 nm, 10 nm, 5 nm, or 1 nm nominally, as measured at 50%of peak output. Each laser diode 152A1, 152B1, and/or 152C1 may comprisea driver configured to deliver about 3.3 kW peak power (nominal) with apulse width of about 150 ns (measured at 50% of amplitude) and arepetition rate of about 10 to about 2000 Hz, or about 0.5% of setting.Each light pulse can be configured to deliver about 0.5 mJ of energy(3300 W×150 ns), nominally. The output of a plurality of laser diodes152A1, 152B1, and/or 152C1 can be combined together into a single fiber.For each light pulse, the laser diode subsystem 135 may be configured tooutput a trigger signal to a digitizer coupled to the laser diodesubsystem 135, such that the digitizer may start the sampling sequence.

While an array of three laser diodes is described, other configurationsare also contemplated. For example, the array may have two laser diodesor four or more laser diodes. Alternatively or in combination to usingan array of laser diodes to produce light output at differentwavelengths, the laser subsystem 135 may comprise an optical parametricoscillator (OPO) to rapidly switch a laser output between multiplewavelengths.

FIG. 3 illustrates the system 100 in use to measure cerebral oxygenation(such as SSS(SO₂)) of a fetus FE present in the uterus UT during labor.As shown in FIG. 3 and described above and herein, the system 100generally comprises an optoacoustic monitor or console 110 and thepatient interface or cerebral oxygenation probe 150 that is connected tothe monitor. The monitor or console 110 may comprises a light sourcesuch as the photodiode subsystem 135 that generates light, such as nearinfrared (NIR) laser light that can, as indicated in FIG. 3, be emittedfrom the tip of the probe 150 and into a fetus' head. The absorption ofthe light's energy in a medium can be followed by thermal expansion ofthe irradiated medium, in this case the blood in the SSS, which inducesmechanical stress that propagates in the form of acoustic (e.g.,ultrasonic) pressure waves. These waves can travel through the braintissue with minimal scattering and can be detected by an acoustic sensorwithin the probe that converts the waves into electrical signals thatcan be provided to the monitor or console 110 and/or to a computer forprocessing.

In some embodiments, the emitted light is within the low end of the NIRspectral range, such as approximately 600 to 1300 nm, for example 760nm, 800 nm, and 860 nm as discussed above and herein. Such a wavelengthrange can result in deep penetration of the NIR radiation, which issufficient for optoacoustic monitoring of hemoglobin saturation. Theamount of laser energy applied for monitoring may be small and cannotinduce any thermal or mechanical damage to a patient's skin or apatient's or operator's ocular tissues because laser fluence levels arewell below the maximum permissible exposures (MPE) for ocular tissues.In some embodiments, the laser energy is delivered at a power ofapproximately 1 μJ to 1mJ.

Oxyhemoglobin and deoxyhemoglobin have high absorption coefficients inthe visible and NIR spectral range. Therefore, both the amplitude andspatial distribution of the generated optoacoustic pressure induced inblood are generally dependent on total hemoglobin concentration [THb]and hemoglobin saturation (calculated as oxyhemoglobin [THb]). The highresolution of the disclosed measurement technique enables directmeasurement of [THb] and saturation in large blood vessels. In someembodiments, saturation can be assessed using an optical parametricoscillator (OPO) pumped by Nd-YAG laser to generate four importantwavelengths: 800 or 805 nm (isosbestic point where oxy- anddeoxyhemoglobin have equal absorption) and 700, 730, and 760 nm, whichare wavelengths at which oxy- and deoxyhemoglobin have strongdifferences in absorption. In some embodiments, the concentration ofdifferent molecules may be of interest such that other wavelengths arechosen. For example, one of the photodiodes 152A1, 152B1, and/or 152C1may be configured to output a light signal at 860 nm, the wavelength atwhich an exogenous dye such as indocyanine green (ICG) shows very lowacoustic response, while at about 900 nm, it has a peak acousticresponse. This contrast may provide high accuracy of ICG monitoring.

The acoustic signal generally returns in a straight line from thetarget. Laser optoacoustic imaging techniques combine the merits ofoptical tomography (high optical contrast) and ultrasound imaging(minimal scattering of acoustic waves) to yield a noninvasive diagnosticmodality with high contrast, sensitivity, and resolution. The highresolution, sensitivity, and contrast of optoacoustic techniques providemonitoring of [THb], oxygenated and deoxygenated hemoglobin withexcellent accuracy, specificity and sensitivity. Transmission ofultrasound signals in a straight line differentiates optoacousticmeasurements from pure optical techniques in which both incident andreturning optical signals are scattered by passage through tissue.Optoacoustic imaging can visualize structures in optically turbid andopaque tissues at depths as great as several centimeters with a spatialresolution <0.5 mm and can reconstruct optoacoustic images. In summary,the merits of optoacoustic monitoring include, but are not limited to:(1) noninvasiveness, (2) accurate, quantitative measurements, (3)continuous, real-time monitoring, (4) high spatial resolution, and (5)compact dimensions.

FIGS. 4-6 illustrate an example a cerebral oxygenation probe 20 that canbe used in the system 10 shown in FIG. 3. The patient interface 150 maycomprise the probe 20. As the probe 20 may be designed to emit light anddetect acoustic waves, the probe can be referred to as an optoacousticprobe. Generally speaking, the probe 20 comprises a head 22 from whichmay extend one or more cables 24 that connect the probe 20 to theremainder of the system 100.

The head 22 can be made of a biocompatible polymeric material such aspolyamide (e.g., PA 2200), polycarbonate (e.g., PC-ISO), oracrylonitrile butadiene styrene (e.g., ABS-M30) and can comprise one ormore pieces. In cases in which the head 22 comprises more than onepiece, the pieces may be sealed together so as to prevent the ingress ofair or fluid into the interior of the head. As is apparent from FIGS.4-6, the head 22 can comprises a generally cylindrical housing 26. Themedial portion of the housing 26 (along its longitudinal axis) can benarrower than the ends of the housing. More particularly, the housing 26may gradually narrow from each housing end so that the center of thehousing is its narrowest point. Because of this a configuration, thehousing 26 may have a rounded hourglass shape that can be seen mostclearly in FIG. 6. This shape can form a continuous rounded groove 28that encircles the center of the housing 26. In some embodiments, thisgroove 28 has a radius of curvature of approximately 5 to 50 mm. Asdescribed below, this groove 28 can facilitate gripping of the head 22during an oxygenation measurement procedure. Although the dimensions ofthe housing 26 can be varied to suit the application and/or the user, insome embodiments, the housing is approximately 5 to 30 mm in height (H),the ends of the housing are approximately 8 to 20 mm in diameter (D),and the center of the housing is approximately 3 to 15 mm in diameter(d) (see FIG. 6). As is also apparent in FIG. 6, the edges of the endsof the housing 26 can be rounded. The head 22 can comprise a flexible orsoft material, or a rigid material having smooth edges, the materialpreferably providing electrical isolation of the electrical componentshoused within the probe 20.

As indicated most clearly in FIGS. 4 and 5, the front end 30 of thehousing 26 is the working end of the probe, which is configured tointerface with the head of the fetus. At this end of the probe 20, thehousing 26 may comprise a circular opening 32 that provides access tothe housing interior. Visible through this opening 30 may be an internalelectromagnetic shield 34 that is positioned behind a cover 36 thatseals the opening 32. Extending from the center of the cover 36 along adirection parallel to the longitudinal axis of the housing 26 may be thetip of an optical waveguide 38. The nature and function of thesecomponents are described below in relation to the cross-sectional viewof FIG. 7.

With further reference to FIGS. 4-6, extending from the housing 26 is astrain relief element 40 that provides strain relief for the cables 24extending from the probe head 22. In some embodiments, the strain reliefelement 40 can be made of the same material as the housing 26 and may beunitarily formed therewith. As shown in FIGS. 4-6, the cables 24 mayinclude an electrical cable 42 and an optical cable 44, which are usedto transmit electrical and optical signals, respectively. It is noted,however, that these cables 42, 44 can be combined into a single cable,if desired. As indicated most clearly in FIG. 6, the strain reliefelement 40 can extend out from the rear end 46 of the housing 26 in adirection that is generally perpendicular to the longitudinal axis ofthe housing. As is apparent from comparison of FIGS. 5 and 6, the stainrelief element 40 can have a width dimension (FIG. 5) that is greaterthan its height dimension (FIG. 6). The optical cable 44 may be flexibleand small (e.g., diameter of about 1 mm), such that the cable can bendto fit in housing.

The housing 26 and the strain relief element 40 can be configured toallow the user to position the probe over the anterior fontanel of afetus head positioned in various orientations, and over a range ofdepths within the birth canal. For example, the probe 20 may bedimensioned to fit between the fetus head and the cervix wall, or to siton top of the fetus head in the cervical opening. The strain reliefelement may be configured to have a flexible or adjustable angle of exitfor the cables, in order to allow the user to move the probe to theappropriate position for measurement.

FIG. 7 illustrates an example construction for the optoacoustic probe 20shown in FIGS. 4-6. As indicated in FIG. 7, the probe head 22 can beformed from two pieces of material that are coupled together to definethe housing 26 and the strain relief 40. Alternatively, the probe head22, including the housing 26 and the strain relief 40, may be formedfrom a single, integral piece of material. More particularly, the head22 can comprise a top portion 50 and a bottom portion 52 that eachdefines part of the housing 26 and the strain relief 40 and that areattached to each other so as to seal a hollow interior space 54 in whichinternal components of the probe reside. As is indicated in FIG. 7,these components include the electromagnetic shield 34, cover 36, andoptical waveguide 38 referenced above, as well as an acoustic sensor 56,a spacer element 58, a printed circuit board (PCB) 60, and an acousticbacking material 62. The purpose of each of these components isdescribed below.

The electromagnetic shield 34 may be an element that surrounds the otherinternal components of the probe 20, including the acoustic sensor 56and the PCB 60, and may shield them from electromagnetic interference.The shield 34 may be made of an electrically conductive material, suchas copper foil, and can act as a shield from electromagnetic noise thatwould otherwise interfere with the proper operation of the probe 20.

The cover 36 can insulate the electromagnetic shield 34 and seals thefront end 30 of the housing 26 to prevent air or liquid from passingthrough its opening 32. In some embodiments, the cover 36 is made of atransparent polymeric material, such as poly(methyl methacrylate).

The optical waveguide 38 can be used to deliver pulsed NIR light to thetissues within the brain of the fetus so as to induce ultrasonic wavesfrom the SSS that can be detected by the acoustic sensor 56. The opticalwaveguide 38 can comprise a single optical fiber or multiple opticalfibers. In the latter case, the optical fibers can be bundled together,as with an optical fiber cable, or can be spatially separated from eachother. In some embodiments, the optical waveguide 38 comprises a singleoptical fiber having a 10 to 1,500 μm core and an outer diameter ofapproximately 12 to 2,000 μm. Irrespective of the particular nature ofthe optical waveguide 38 that is used, the tip of the waveguide extendsbeyond the outer surface of the cover 36. This extension can facilitateplacing the optical waveguide 38 in direct contact with the scalp incases in which the fetus has a significant amount of hair. In someembodiments, the tip extends approximately 1 to 3 mm beyond the outersurface of the cover 36. For example, the optical waveguide may comprisea plurality of optical fibers having a diameter of about 1 mm,protruding from the housing to form a “brush” of fibers that can passthrough the hair to contact the scalp, thereby reducing loss of lightintensity due to absorption by the hair. The optical fibers may extendthrough the center of the bottom of the housing as shown in FIG. 7, andextend about 2 mm beyond the outer surface of the cover 36. Theplurality of fibers may be spaced center-to-center in such a way thatthe fibers can be located over the SSS. The fibers are preferablyconfigured to be comfortable for up to 24 hours of continuous contactwith the target tissue.

As mentioned above, the acoustic sensor 56 can detect the ultrasonicwaves that are generated by the SSS of the fetus. In some embodiments,the acoustic sensor 56 comprises a piezoelectric transducer that usesthe piezoelectric effect to measure changes in pressure, acceleration,strain, or force and convert them into an electrical signal. The sensor56 may be separated from the electromagnetic shield 34 by the spacerelement 58, which can be made of a polymeric material, such aspolyamide. In some embodiments, the spacer element 58 is approximately0.005 to 5 mm thick.

The electrical signals generated by the acoustic sensor 56 aretransmitted to the PCB 60 via one or more electrical wires 64. The PCB60 comprises a preamplifier that amplifies the signals received from thesensor 56 before transmitting them to a monitor or computer of thesystem along further electrical wires 66. The preamplifier can beconfigured to provide about 40 dB of gain at about 500 kHz, having abandwidth of about 3 dB in the range from about 40 kHz to about 10 MHz.The PCB may further comprise a digitizer configured to digitize theacoustic signal detected by the acoustic sensor 56. For example, thedigitizer can be configured to sample the acoustic signal from thepreamplifier at least at about 20 MHz, in response to a trigger signalfrom the laser diode subsystem connected to the probe, as describedherein. The digitizer can, for example, store about 1000 samples of theacoustic signal, and transfer the block of samples to the processor ofthe console unit 100 connected to and controlling the operation of theoptoacoustic probe, for waveform averaging of the samples.

The acoustic backing material 62 is positioned behind the acousticsensor 56. It provides backing for the sensor 56 (for wideband detectionof pressure waves) and absorbs the vibrations that travel through thesensor to prevent undesired ringing in the signal and separate part ofthe signal from ringing noise. In some embodiments, the attenuator 62comprises a mass of epoxy.

The hollow interior space 54, within which the internal components ofthe probe reside, may be substantially cylindrical as shown in FIG. 7,with a diameter 54 d in a range from about 8 to about 10 mm, and aheight 54 h of about 10 mm.

The probe 20 may be designed to reduce areas that cannot be easilycleaned and disinfected between uses, such as grooves or pockets of inthe exterior surface of the housing. Alternatively or in combination,the probe 20 may comprise a disposable cover configured to be placedover the housing, in order to reduce the need for cleaning anddisinfecting the probe between uses. The probe 20 is preferablyconfigured such that its components can withstand soaking in adisinfecting solution for sterilization.

FIGS. 11A and 11B illustrate an exemplary configuration of anoptoacoustic probe 20 as described herein. The probe 20 may comprise ahead 22 extending from a cable bundle 24 connected to a console thatcontrols operation of the probe, such as console 110 described inreference to FIGS. 1 and 2. The head 22 can comprise a housing 26, a topportion 50, and a bottom portion 52 comprising substantially the sameshape. For example, the housing 26 can have a substantially cylindricalshape, for example with a diameter D in a range from about 30 mm toabout 40 mm and a height H of about 18 mm. The top portion 50 and bottomportion 52 may be substantially circular with substantially the samediameter D, oriented substantially parallel to one another. The housingcan comprise an annular groove 28 extending continuously about the sideof the housing at the center portion of the housing. The groove 28 canform a concave side surface of the housing that facilitates gripping ofthe probe head 22 by the user while the user places the bottom portion52 in contact with the target tissue for oxygenation measurement.

FIGS. 12A and 12B illustrate another exemplary configuration of anoptoacoustic probe 20 as described herein. The probe 20 may comprise ahead 22 extending from a cable bundle 24 connected to a console thatcontrols operation of the probe, such as console 110 described inreference to FIGS. 1 and 2. The head 22 can comprise a housing 27 havinga top portion 51 and a bottom portion 53 comprising different shapes.For example, the bottom portion 53 may comprise a substantially circularshape having a diameter D, while the top portion 51 may comprise anelongated shape extending over the diameter D of the bottom portion. Theplane of the top portion 51 may be disposed at an angle 55 with respectto the plane of the bottom portion 53, such that a first end 51 a of thetop portion connects directly to the bottom portion 53. The maximumheight H of the housing may be about 25 mm, and the diameter D of thebottom portion may be about 30 mm to about 40 mm. The housing maycomprise a groove 29 extending continuously about a portion of the sideof the housing. As shown in FIG. 12B, the groove 29 may have a taperthat corresponds to the angle 55 between the top portion 51 and bottomportion 53 of the housing, such that the groove terminates at the pointthe first end 51 a of the top portion connects with the bottom portion.The groove 29 may form concave rear and side surfaces of the housingthat facilitate gripping of the probe head 22 by the user while the userplaces the bottom portion 53 in contact with the target tissue foroxygenation measurement. The strain relief element 40, coupled to theprobe head 22 and configured to relieve strain placed on the cables 24,may have a streamlined or tapered shape as shown.

FIGS. 8 and 9 illustrate two examples of the manner in which the probe20 can be grasped by an obstetrician during a fetal cerebral oxygenationmeasurement procedure. In both cases, the head 22 of the probe ispinched between the tips of the index and middle fingers. As shown inthe figures, the groove 28 within the probe head housing 26 facilitatesthe pinch grip. The cable(s) 24 of the probe 20 can be run either alongthe inside of the hand, as indicated in FIG. 8, or along the outside ofthe hand, as indicated in FIG. 9. Once the desired grip and cablerouting have been attained, the obstetrician can then insert his handthrough the vagina and into the birth canal to place the front end ofthe probe head 22 in contact with the head of the fetus, as illustratedin FIG. 3. Measurements can then be obtained using the probe 20 andprocessed to determine cerebral oxygenation. Preferably, the probe head22 is placed over the anterior fontanel of the head of the fetus,wherein the fetus is in any head down position (e.g., direct occiputanterior (OA), left occiput anterior (LOA), right occiput anterior(ROA), left occiput transverse (LOT), right occiput transverse (ROT),direct occiput posterior (OP), left occiput posterior (LOP), rightocciput posterior (ROP)). In a typical scenario, the fetus's head may berecessed about 50 mm into the birth canal and the cervix may be dilatedto about 4 to 5 cm. The insertion, positioning, and measurement with theoptoacoustic probe can have a duration of about 30 to about 45 seconds,for example.

The probe 20 may be used with ultrasound gel, or may be used withoutultrasound gel with the probe head in close contact with the fetalscalp. If used without ultrasound gel, the inherent moisture in theenvironment surrounding the probe head may provide adequate acousticcoupling.

FIGS. 13A-13C illustrate an exemplary configuration of a probe 20 asgrasped by a user during a fetal cerebral oxygenation measurementprocedure. The probe 20 may comprise a probe head 22 having a shape asillustrated in FIGS. 12A-12B, wherein the top portion 51 and the bottomportion 53 of the housing comprise different shapes. The probe head 22can be grasped between the index and middle fingers of the user, withthe distal portions of the fingers engaging a groove 29 in the housingof the head as described herein. The cable bundle 24 can be run alongthe inside of the hand, as shown in FIGS. 13B and 13C. The head 22 maybe compactly sized to easily fit within the distal portions of theuser's fingers. For example, the length 70 from the tip of the head 22to the end of the strain relief element 40 may be about 40 mm, as shownin FIG. 13A. The bottom portion 53 of the housing of the head may have athickness 71 of about 10 mm, as shown in FIG. 13B. The diameter D of thebottom portion of the housing may be about 18 mm to about 20 mm, asshown in FIG. 13C.

FIGS. 14A-14C illustrate another exemplary configuration of a probe 20as grasped by a user during a fetal cerebral oxygenation measurementprocedure. The probe 20 may comprise a probe head 22 having a shape asillustrated in FIGS. 11A-11B, wherein the top portion 50 and the bottomportion 52 of the housing comprise substantially the same circularshape. The probe head 22 can be grasped between the index and middlefingers of the user, with the distal portions of the fingers engaging agroove 28 in the housing of the head as described herein. The cablebundle 24 be run along the inside of the hand, as shown in FIGS. 14B and14C. The head 22 may be compactly sized to easily fit within the distalportions of the user's fingers. For example, the length 72 from the tipof the head 22 to the end of the strain relief element 40 may be about20 mm to about 30 mm, as shown in FIG. 14A. The bottom portion 52 of thehousing of the head may have a thickness 73 of about 10 mm, as shown inFIG. 14B. The diameter D of the bottom portion of the housing may beabout 18 mm to about 20 mm, as shown in FIG. 14C.

FIGS. 15A and 15B illustrate another exemplary configuration of a probe20 as grasped by a user during a fetal cerebral oxygenation measurementprocedure. The probe 20 may comprise a probe head 22 and strain reliefelement 40 as described herein, wherein the head 22 may comprise ahousing having a groove, such as groove 28 or 29 as shown in FIGS. 11Band 12B. The user may grasp the head 22 with two fingers as describedherein, or the user may place the tip of a single finger within thegroove. As shown in FIG. 15A, a finger cot 80 may be placed over the oneor two fingers engaging the head 22, in order to securely couple thehead to the one or two fingers of the user. The head 22 disposed withinthe finger cot 80 may have a height 81 of about 40 mm, with the bottomportion of the housing having a diameter D of about 20 mm. A portion ofthe cables 24, extending out of the strain relief element 40, may beenclosed within the finger cot 80, with the remainder of the cableconfigured to be run along the inside of the hand. Alternatively, asshown in FIG. 15B, a finger glove 82 may be placed over the one or twofingers of the user engaging the probe head 22, wherein the finger glovemay have straps that are secured around the wrist of the user in orderto securely couple the finger glove to the user's hand. To facilitateinsertion of the finger and the probe head into the finger glove 82 orfinger cot 80, the probe head 22 may comprise a tapered “bull-nose”shape on the tip of the head, as shown in FIG. 15B. The strain relief 40may also comprise a tapered bull-nose shape, so as to further relievetension placed on the cables 24. The housing of the probe may comprisethe bull-nose shape as shown, or alternatively, an adaptor may be placedover the housing to provide the bull-nose shape. The bull-nose shapedprobe head 22 of FIG. 15B can have a height 83 of about 40 mm, a bottomdiameter D of about 20 mm, and a maximum diameter 84 of about 30 mm toabout 35 mm.

FIGS. 17A-17C show a further embodiment of the probe 20. In thisembodiment, the probe 20 may comprise a housing 26 which may include acontinuous rounded groove 28 that encircles the center of the housing26. The housing 26 may further comprise a finger pocket 117 where a usercan place his or her finger to manipulate and position the probe 20while using another finger to palpate for the SSS or fontanel on thefetus. The finger pocket 117 may be located on one end of the probe 20while the light output and acoustic transducer is located on the otherend as described above and herein. The cables 24 may extend in astraight manner proximally from the housing 26 (FIG. 17B) or at an angle(FIG. 17C).

FIG. 16 shows a flowchart of a method 160 of determining one or morephysiological parameters optoacoustically.

In a step 1600, a measurement sequence may be started.

In a step 1605, the temperatures of the first, second, and third lightpulse generators may be managed as described above and herein. Forexample, the temperatures may be managed to keep the light pulsegenerators in an optimal temperature range for operation, for example,10° C. to 40° C. The first, second, and third light pulse generators maycomprise laser diodes (for example, laser diodes 152A1, 152B1, and/or152B1 described above) for which the stability of the light outputfrequency is dependent on temperature. The step 1605 may comprisesub-steps of continuously measuring the temperatures of the first,second, and third light pulse generators; directing a cooling aircurrent (from cooling fan 160, for example) to the first, second, andthird light pulse generators; activating first, second, and thirdthermoelectric coolers (for example, thermoelectric coolers 152A2,152B2, and/or 152C2 described above) coupled to the first, second, andthird light pulse generators, respectively, to direct heat away from thefirst, second, and third light pulse generators; and, adjusting thecooling air current and thermoelectric coolers to maintain the first,second, and third light pulse generators in the optimal, operationaltemperature range. In a step 1610, a first light pulse train may begenerated as described above and herein, and the first light pulse trainmay have a first wavelength.

In a step 1620, each light pulse of the generated pulse train may bedirected onto tissue as described above and herein. The generated lightpulses may be directed onto the tissue of interest such as with apatient interface device, for example, the patient interface 150described above and/or the optoacoustic probe 14. The step 1610 maycomprise sub-steps of providing the handheld probe 20 and positioningthe probe 20 adjacent the tissue of interest to be interrogated such asthe anterior fontanel of a fetus as described above).

In a step 1622, the acoustic response from the tissue can be measured asdescribed above and herein. The acoustic response may comprise theacoustic response of the superior sagittal sinus of the fetus asdescribed above. As described above, for example, the acoustic responsemay be captured with an acoustic sensor 56 of the probe 20 or othereffector portion of the patient interface 150.

In a step 1624, the acoustic response from each light pulse may beamplified and digitized as described above and herein. As describedabove, for example, the electrical signals generated by the acousticsensor 56 may be amplified with a preamplifier of the probe 20. Thepreamplified signals may be received by the acoustic subsystem 140 ofthe console unit 100. The preamplified signals may then be furtheramplified by the acoustic subsystem 140 and then sampled with adigitizer. The sampled signals may then be transferred to the processor115 of the console 110 for waveform averaging to extract the waveformout of background noise.

In a step 1626, the acoustic response waveform for the pulse train maybe averaged as described above and herein.

In a step 1628, the amplitude of the wavelet for the acoustic responsefrom the blood analyte can be detected as described above and herein.

In a step 1630, a second light pulse train may be generated as describedand herein, and the second light pulse train may have a secondwavelength different from the first wavelength.

In a step 1635, the steps 1620 through 1628 may be repeated for thesecond wavelength.

In a step 1640, a third light pulse train may be generated as describedand herein, and the third light pulse train may have a third wavelengthdifferent from the first and second wavelengths.

In a step 1645, the steps 1620 through 1628 may be repeated for thesecond wavelength. As described herein and above, the first, second, andthird wavelengths may be different from one another and may be selectedto match the absorption peak and acoustic response peak of the targetparameter of interest. As described herein and above, exemplarywavelengths include 700 nm, 730 nm, 760 nm, 800 nm, 805 nm, and 860 nm,to name a few. For example, the first wavelength may be 800 nm or 805nm, the isosbestic point where oxyhemoglobin and deoxyhemoglobin haveequal absorption and the second and third wavelengths may be wavelengthswhere oxyhemoglobin and deoxyhemoglobin have strong differences inabsorption such as 700 nm, 730 nm, and 760 nm.

In a step 1650, the physiological parameter(s) may be determined fromthe acoustic response. The processor 115 of the console unit 100 may beconfigured to make such a determination. For example, the physiologicalparameter(s) of interest, such as blood oxygenation or SSS(SO₂), may bedetermined by comparing the acoustic response at two differentwavelengths of the light pulses. To provide a more accurate and reliablereading of the physiological parameter(s) of interest, two or more ofthe determined physiological parameter(s) may be averaged together asdescribed herein.

In a step 1655, the determined physiological parameter(s) may bedisplayed as described above and herein, such as with a display 125 ofthe console unit 100 as described above. In some embodiments, theaveraged physiological parameter(s) are displayed.

In a step 1660, the determined physiological parameter(s) may be storedin a memory. For example, the physiological parameter(s) measured may beelectronically sent to an electronic health record management system bythe console unit 100.

In a step 1670, the user may be queried as to whether to continuemeasurements. If the user desires to continue the measurements, themeasurement sequence may be restarted with the step 1600. In the userdesires to end the measurements, the measurement sequence may be stoppedwith the step 1680. It can be determined whether further steps arenecessary may be determined. For example, a physician or other medicalprofessional can make a determination of whether a caesarian procedureis necessary based on the measured blood oxygenation shown by theconsole unit 100. Alternatively or in combination, the console unit 100may be configured to make and show a recommendation as to whether acaesarian or other procedure is necessary based on the measured bloodoxygenation shown.

Although the above steps show the method 160 of determining one or morephysiological parameters optoacoustically in accordance with manyembodiments, a person of ordinary skill in the art will recognize manyvariations based on the teaching described herein. The steps may becompleted in a different order. Steps may be added or deleted. Forexample, oxygenation or other physiological parameter of interest may bedetermined using pulse trains of light at two or fewer wavelengths. Someof the steps may comprise sub-steps. Many of the steps may be repeatedas often as beneficial to the diagnostic measurement(s).

One or more of the steps of the method 160 may be performed with variouscircuitry, as described herein, for example one or more of theprocessor, controller, or circuit board described above and herein. Suchcircuitry may be programmed to provide one or more steps of the method1600, and the program may comprise program instructions stored on acomputer readable memory or programmed steps of the logic circuitry suchas programmable array logic or a field programmable gate array, forexample.

Aspects of the present disclosure also include methods of measuringoxygenation. Such methods include the application of formulas to measureoxygenation when signals are good (i.e., there is low background).Exemplary formulas to determine blood oxygenation at differentwavelengths of light signals are listed below, where R is the ratio ofoptoacoustic amplitudes at 760 and 800 nm (R=A₇₆₀/A₈₀₀).

760 nm:SO ₂=1.54−0.76·R→R=2.02−1.31·SO ₂

850 nm:SO ₂=−2.42+2.66·R→R=0.91+0.38·SO ₂

In general, for any wavelength: R=a′_(i)+b′_(i)·SO₂

For instance, introducing 1.0 to generate a difference of signals wouldyield:

R − 1 = a_(i) + b_(i) ⋅ SO₂ − 1${\frac{A_{760}}{A_{800}} - 1} = {a_{i}^{\cdot} + {b_{i}^{\cdot} \cdot {SO}_{2}} - 1}$

And, the differential signal D₇₆₀=A₇₆₀−A₈₀₀ may be represented by theequation:

$\frac{A_{760} - A_{800}}{A_{800}} = {{{b_{i}^{\prime}{SO}_{2}} + {a_{i}^{\prime} \cdot \cdot 1}} = {{{{- 1.31} \times {SO}_{2}} + 2.02 - 1} = {{{- 1.31} \cdot {SO}_{2}} + 1.02}}}$

So, in general, for any wavelength, the below equation (Eq. 1) mayapply:

$\frac{A_{i} - A_{800}}{A_{800}} = {{b_{i}^{\prime}{SO}_{2}} + {a_{i}^{\prime} \cdot \cdot 1}}$

And, a third wavelength (e.g. 850 nm) may be introduced to remove A₈₀₀as follows with the following equation (Eq. 2):

$\frac{A_{850} - A_{800}}{A_{800}} = {{{0.38 \cdot {SO}_{2}} + 0.91 - 1} = {{0.38 \cdot {SO}_{2}} - 0.09}}$

To remove A₈₀₀, Eq. 1 may be divided by Eq. 2 as follows.

$\mspace{20mu} {{{RDS} \equiv \frac{A_{760} - A_{800}}{A_{850} - A_{800}}} = \frac{{{- 1.31} \cdot {SO}_{2}} + 1.02}{{0.38 \cdot {SO}_{2}} - 0.09}}$(0.38 ⋅ SO₂ − 0.09) ⋅ (A₇₆₀ − A₈₀₀) = (−1.31 ⋅ SO₂ + 1.02) ⋅ (A₈₅₀ − A₈₀₀)  And  where  D₇₆₀ = A₇₆₀ − A₈₀₀  and  D₈₅₀ = A₈₅₀ − A₈₀₀  0.38 ⋅ D₇₆₀ ⋅ SO₂ − 0.09 ⋅ D₇₆₀ = −1.31 ⋅ D₈₅₀ ⋅ SO₂ + 1.02 ⋅ D₈₅₀  0.38 ⋅ D₇₆₀ ⋅ SO₂ + 1.31 ⋅ D₈₅₀ ⋅ SO₂ = 1.02 ⋅ D₈₅₀ + 0.09 ⋅ D₇₆₀  SO₂(0.38 ⋅ D₇₆₀ + 1.31 ⋅ D₈₅₀) = 1.02 ⋅ D₈₅₀ + 0.09 ⋅ D₇₆₀$\mspace{20mu} {{SO}_{2} = \frac{{1.02 \cdot D_{850}} + {0.09 \cdot D_{760}}}{{0.38 \cdot D_{760}} + {1.31 \cdot D_{850}}}}$

The last above equation for SO₂ can be used to measure oxygenation usingany (bad or good) signals with high background from hair or skinmelanin, for instance, (such as in fetuses, neonatal and adult heads,and dark skin). Therefore, three or more wavelengths of light signals ortwo or more wavelength pairs for light signals may be used to measureoxygenation optoacoustically, even in conditions of high background. Thewavelengths noted above are examples only, and other wavelengths arealso contemplated for use as described above and herein. The abovecoefficients for the various formulas and equations are examples only aswell, and other coefficients for the above formulas and equations arealso contemplated for use.

Experimental Data

In an experimental procedure, hemodynamically stable neonates wereoptoacoustically measured in order to simulate optoacoustic monitoringof a fetus. An optical parametric oscillator (OPO) was controlled by apersonal computer that was programmed to rapidly switch between threewavelengths: 800 nm (isobestic point), 760 nm, and 700 nm at an energylevel of 15 microjoules, similar to the energy produced by pulsed laserdiodes. SSS(SO₂) was then calculated from each of two pairs ofwavelengths (760 nm and 800 nm) and (700 nm and 800 nm) and then themean of the two calculations was determined. By taking the mean of twoor more calculations, a more accurate measurement of blood oxygenationcan be made.

In the first of two neonates (Baby 1: weight 1,795 g; current weight2,885 g; gestational age 32 wks), at two time intervals, SSS(SO₂) was58% and 69%. In the second neonate (Baby 2: weight 3,040 g; gestationalage 39 wks), at three time intervals, SSS(SO₂) was 55%, 60%, and 62%.These measurements are consistent with the expected ranges and withphysiologic changes over time. FIGS. 10A and 10B show the raw data fromwhich SSS(SO₂) was calculated for Babies 1 and 2.

While measurements at three different wavelengths can be taken, it isnoted that measurements can be taken at other numbers of wavelengths.For example, in some embodiments, measurements can be taken at 760 nmand 800 nm. Furthermore, while the optoacoustic probe described hereincomprises an optical waveguide that turns light generated by a lightsource through 90°, it is noted that the light can be emitted from theprobe at any angle from 0° (i.e., straight from the tip of the probe) to90°. The particular angle that is used may depend upon which angleprovides the easiest access to the fetal head and fontanel dependingupon fetal head position and anatomy.

In another experimental procedure, acoustic signals were measured from afetus during late stage labor. The acoustic response was generated bydirecting light signals to tissue at 760 nm, 800 nm, and 850 nm. FIG.18A shows a measured differential signal where the signal obtained at800 nm was subtracted from the signal obtained at 760 nm. FIG. 18B showsa measured differential signal where the signal obtained at 800 nm wassubtracted from the signal obtained at 850 nm. The two peaks shown ineach graph may represent the acoustic response from skin and theacoustic response from the superior sagittal sinus (SSS). The peak fromthe SSS may be used to determine the venous oxygenation of the fetus atthe SSS.

While preferred embodiments of the present disclosure have been shownand described herein, it will be obvious to those skilled in the artthat such embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will now occur to those skilledin the art without departing from the scope of the present disclosure.It should be understood that various alternatives to the embodiments ofthe present disclosure described herein may be employed in practicingthe inventions of the present disclosure. It is intended that thefollowing claims define the scope of the invention and that methods andstructures within the scope of these claims and their equivalents becovered thereby.

We claim:
 1. A method of measuring hemoglobin concentration in a fetus,the method comprising: inserting a sensor into a vagina, the sensorcomprising a light output and an acoustic transducer; and positioningthe sensor over an anterior fontanel of a head of the fetus, wherein thelight output of the sensor emits light to the head of the fetus and theacoustic transducer of the sensor detects acoustic pressure generated inresponse to the emitted light, and wherein the sensor determineshemoglobin concentration in the fetus in response to the detectedacoustic pressure.
 2. The method of claim 1, wherein the sensorcomprises a probe head, and wherein inserting the sensor into the vaginacomprises inserting the probe head of the sensor into the vagina.
 3. Themethod of claim 2, wherein the sensor comprises hemoglobin concentrationmonitor configured to display the determined hemoglobin concentration ofthe fetus and a cable connecting the probe head with the hemoglobinconcentration monitor.
 4. The method of claim 3, wherein the hemoglobinconcentration monitor and at least a portion of the cable remain outsidethe uterus as the probe head is inserted into the vagina.
 5. The methodof claim 3, wherein the light output comprises a waveguide in the probehead, wherein the cable comprises one or more optical fibers, andwherein the hemoglobin concentration monitor comprises one or more laserdiodes or light emitting diodes coupled to the waveguide through the oneor more optical fibers.
 6. The method of claim 2, wherein inserting thesensor into the vagina comprises grasping the probe head between twofinger tips of a user.
 7. The method of claim 2, wherein positioning thesensor over a head of the fetus comprises positioning the light outputand the acoustic transducer to face a superior sagittal sinus of thefetus.
 8. The method of claim 7, wherein the light output of the sensoremits light to a superior sagittal sinus of the fetus through theanterior fontanel, wherein the acoustic pressure generated in responseto the emitted light is generated by the superior sagittal sinus, andwherein the sensor determines a hemoglobin concentration at the superiorsagittal sinus.
 9. The method of any of claim 1, wherein positioning thesensor over the anterior fontanel of the head of the fetus comprisescontacting a tip of the light output extending from the probe head toskin of the head of the fetus.
 10. The method of claim 1, wherein sensordetermines hemoglobin concentration continuously.
 11. A method ofmeasuring hemoglobin concentration in a fetus, the method comprising:emitting light from a light output of a sensor positioned over ananterior fontanel of a head of a fetus; detecting acoustic pressure withan acoustic transducer of the sensor, the acoustic pressure beinggenerated in response to the emitted light; measuring hemoglobinconcentration in the fetus in response to the detected acousticpressure; and displaying the measuring hemoglobin concentration in thefetus to the user with the sensor.
 12. The method of claim 11, whereinthe sensor comprises a probe head comprising the light output andacoustic transducer, and wherein detecting the acoustic pressure withthe acoustic transducer comprises detecting the acoustic pressure withthe probe head positioned over the anterior fontanel of the fetus. 13.The method of claim 12, wherein the light output comprises a tipextending out from an outer body of the probe head, and wherein emittingthe light comprises emitting the light through the tip of the lightoutput positioned over the anterior fontanel of the fetus.
 14. Themethod of claim 12, wherein displaying the measured hemoglobinconcentration comprises displaying the determined hemoglobinconcentration with a hemoglobin concentration monitor of the sensor, themonitor being coupled to the probe head with a cable.
 15. The method ofclaim 14, wherein emitting the light comprises emitting the lightthrough a waveguide in the probe head, wherein the cable comprises oneor more optical fibers, and wherein the hemoglobin concentration monitorcomprises one or more laser diodes or light emitting diodes coupled tothe waveguide through the one or more optical fibers.
 16. The method ofclaim 11, wherein emitting the light comprises emitting the light withthe light output and the acoustic transducer facing a superior sagittalsinus of the fetus.
 17. The method of claim 11, wherein emitting thelight comprises emitting the light to a superior sagittal sinus of thefetus, wherein the acoustic pressure generated in response to theemitted light is generated by the superior sagittal sinus.
 18. Themethod of claim 11, wherein hemoglobin concentration is measuredcontinuously.
 19. A system for measuring hemoglobin concentration in afetus, the system comprising: a monitor comprising a processor, a lightsource, and a display; a cable; and a probe head comprising a housinghaving one or more lateral grooves adapted to accommodate finger tipssuch that the probe head is configured to be held between two fingertips of a user, the probe head being coupled to the monitor through thecable and further comprising a light output and an acoustic transducer,wherein the probe head has a vertical axis, wherein the one or morelateral grooves are oriented in a first transverse direction to thevertical axis and the cable is oriented in a second transverse directionto the vertical axis to facilitate handling and insertion of the probehead and cable by two fingers of a user, wherein the light source isconfigured to generate a light emitted to the fetus through the lightoutput of the probe head, wherein the acoustic transducer is configuredto detect acoustic pressure generated in response to the emitted light,wherein the processor is configured to determine hemoglobinconcentration in the fetus in response to the detected acousticpressure, and wherein the display is configured to display thedetermined hemoglobin concentration.
 20. The system of claim 19, whereinthe light output comprises a tip extending out from an outer body of theprobe head.
 21. The system of claim 19, wherein the light source of themonitor comprises one or more laser diodes or light emitting diodes. 22.The system of claim 19, wherein the cable comprises one or more opticalfibers configured to direct light generated by the light source to thelight emitter of the probe head.
 23. The probe of claim 19, wherein theprobe head further comprises a finger pocket transverse to the verticalaxis of the probe head and disposed at a location opposite one or moreof the light output or acoustic transducers.
 24. A desktop-sized consolefor measuring hemoglobin concentration in a subject, said consolecomprising: a laser diode subsystem for emitting light pulses directedto tissue of a subject, the laser diode subsystem comprising: a firstlaser diode configured to emit a first light pulse at a first outputwavelength, a first thermoelectric cooler coupled to the first laserdiode to regulate a temperature of the first laser diode, a firstcooling fan, and at least one controller coupled to and configured tocontrol the first cooling fan and the first thermoelectric cooler toregulate the temperatures of the first laser diode to stabilize theoutput wavelengths of the first laser diode within an optimal range; anacoustic sensor subsystem for measuring acoustic pressure generated inthe tissue in response to the emitted light pulse; and a processorcoupled to the laser diode subsystem to control the laser diodesubsystem and coupled to the acoustic sensor subsystem to receive themeasured acoustic pressure, wherein the processor is configured todetermine hemoglobin concentration of the subject in response to thereceived acoustic pressure.
 25. The console of claim 24, wherein thelaser diode subsystem further comprises a second laser diode configuredto emit a second light pulse at a second output wavelength differentfrom the first output wavelength and a second thermoelectric coolercoupled to the second laser diode to regulate a temperature of thesecond laser diode, and wherein the at least one controller is furthercoupled to the second thermoelectric cooler to regulate the temperatureof the second laser diode and to stabilize the output wavelength of thesecond laser diode within an optimal range.
 26. The console of claim 25,wherein the laser diode subsystem further comprises a third laser diodeconfigured to emit a third light pulse at a third output wavelengthdifferent from the first and second output wavelengths and a thirdthermoelectric cooler coupled to the third laser diode to regulate atemperature of the third laser diode, and wherein the at least onecontroller is further coupled to the third thermoelectric cooler toregulate the temperature of the third laser diode and to stabilize theoutput wavelength of the third laser diode within an optimal range. 27.The console of claim 26, wherein the laser diode subsystem furthercomprises a first temperature sensor to measure the temperature of thefirst laser diode, a second temperature sensor to measure thetemperature of the second laser diode, and a third temperature sensor tomeasure the temperature of the third laser diode, and wherein the atleast one controller is configured to regulate the temperatures of thefirst, second, and third laser diodes in response to the temperaturesmeasured by the first, second, and third temperature sensors.
 28. Theconsole of claim 26, wherein the first, second, or third wavelength isat an isosbestic point of oxyhemoglobin and deoxyhemoglobin.
 29. Theconsole of claim 26, wherein the first, second, or third wavelength isin a range of 685 nm to 715 nm, 715 nm to 745 nm, 745 nm to 775 nm, 790nm to 820 nm, 845 nm to 875 nm, or 875 nm to 950 nm.
 30. The console ofclaim 24, wherein the laser diode subsystem further comprises a firsttemperature sensor to measure the temperature of the first laser diode,and wherein the controller is configured to regulate the temperatures ofthe first laser diode in response to the temperatures measured by thefirst temperature sensor.
 31. The console of claim 24, wherein the firstwavelength is at an isosbestic point of oxyhemoglobin anddeoxyhemoglobin.
 32. The console of claim 24, wherein the firstwavelength is in a range of 685 nm to 715 nm, 715 nm to 745 nm, 745 nmto 775 nm, 790 nm to 820 nm, 845 nm to 875 nm, or 875 nm to 950 nm. 33.The console of claim 24, further comprising a power supply coupled tothe laser diode subsystem, the acoustic sensor subsystem, and theprocessor.
 34. The console of claim 24, further comprising a displaycoupled to the processor to display the determined hemoglobinconcentration to a user.
 35. The console of claim 34, wherein thedisplay comprises a touch screen for operating the console.
 36. Theconsole of claim 24, further comprising a desktop-sized housingenclosing the laser diode subsystem, the acoustic sensor subsystem, andthe processor.
 37. The console of claim 36, further comprising a secondcooling fan coupled to one or more of the processor or acoustic sensorsubsystem for cooling the console.
 38. The console of claim 24, whereinthe processor is further configured to read or write to medical recordsof the subject.
 39. The console of claim 24, further comprising anoutput port for the laser diode subsystem and an input port for theacoustic sensor subsystem.
 40. The console of claim 39, wherein theoutput port and the input port are configured to be coupled to a sensormodule or an optoacoustic probe to emit the first light pulse to thetissue of the subject and to receive the acoustic pressure generated inthe tissue.
 41. The console of claim 40, wherein the output port and theinput port are configured to be coupled to the sensor module oroptoacoustic probe with a cable comprising one or more optical fibers.42. A method of measuring hemoglobin concentration in a subject, saidmethod comprising: generating, with a first laser diode, a first lightpulse at a first output wavelength; regulating temperatures of the firstlaser diode to stabilize the output wavelengths of the first laser diodewithin an optimal range, wherein the temperatures are regulated with afirst thermoelectric cooler coupled to the first laser diode and a firstcooling fan; directing the generated first light pulse to tissue of asubject; measuring acoustic pressure generated in the tissue in responseto the directed first light pulse; and determining hemoglobinconcentration in the subject in response to the measured acousticpressure.
 43. The method of claim 42, further comprising: generating,with a second laser diode, a second light pulse having a second outputwavelength different from the first output wavelength; regulating atemperature of the second laser diode to stabilize the outputwavelengths of the second laser diode within an optimal range, whereinthe temperatures are regulated with a second thermoelectric coolercoupled to the second laser diode and the first cooling fan; anddirecting the generated second light pulse to the tissue of the subject,wherein the measured acoustic pressure is generated in the tissue inresponse to the directed first and second light pulses.
 44. The methodof claim 43, further comprising: generating, with a third laser diode, athird light pulse having a third output wavelength different from thefirst and second output wavelengths; regulating a temperature of thethird laser diode to stabilize the output wavelengths of the third laserdiodes within an optimal range, wherein the temperatures are regulatedwith a third thermoelectric cooler coupled to the third laser diode andthe first cooling fan; and directing the generated third light pulse tothe tissue of the subject, wherein the measured acoustic pressure isgenerated in the tissue in response to the directed first, second, andthird light pulses.
 45. The method of claim 44, further comprisingmeasuring the temperature of the first laser diode, measuring thetemperature of the second laser diode, measuring the temperature of thethird laser diode, and regulating the temperatures of the first, second,and third laser diodes in response to the temperatures measured.
 46. Themethod of claim 44, wherein the first, second, or third wavelength is atan isosbestic point of oxyhemoglobin and deoxyhemoglobin.
 47. The methodof claim 44, wherein the first, second, or third wavelength is in arange of 685 nm to 715 nm, 715 nm to 745 nm, 745 nm to 775 nm, 790 nm to820 nm, 845 nm to 875 nm, or 875 nm to 950 nm.
 48. The method of claim42, further comprising measuring the temperature of the first laserdiode and regulating the temperatures of the first laser diode isregulated in response to the temperature measured.
 49. The method ofclaim 42, wherein the first wavelength is at an isosbestic point ofoxyhemoglobin and deoxyhemoglobin.
 50. The method of claim 42, whereinthe first wavelength is in a range of 685 nm to 715 nm, 715 nm to 745nm, 745 nm to 775 nm, 790 nm to 820 nm, 845 nm to 875 nm, or 875 nm to950 nm.
 51. The method of claim 42, further comprising displaying thedetermined hemoglobin concentration of the subject.
 52. The method ofclaim 42, further comprising regulating the temperature of the firstlaser diode with a second cooling fan.
 53. The method of claim 52,wherein the second cooling fan is enclosed within a housing enclosingthe first laser diode and the first cooling fan.
 54. The method of claim42, wherein directing the generated first light pulse to tissue of thesubject comprises directing the first light pulse with an opticalwaveguide of a sensor module or an optoacoustic sensor coupled to thefirst laser diode.
 55. The method of claim 54, wherein the acousticpressure is measured by an acoustic transducer of the sensor module orthe optoacoustic sensor.